Propofol with cysteine

Abstract

The present invention relates to pharmaceutical compositions comprising 2,6-diisopropylphenol (propofol). Compositions of the present invention comprise aqueous and non-aqueous compositions of propofol and cysteine or a salt thereof. The propofol containing compositions are preferably sterile and are parenterally administered to any animal, including humans.

We claim:  
     
         1 . A pharmaceutical composition comprising propofol and cysteine.  
     
     
         2 . The pharmaceutical composition of  claim 1 , further comprising one or more excipients.  
     
     
         3 . The pharmaceutical composition of  claim 1 , further comprising a GRAS excipient.  
     
     
         4 . The pharmaceutical composition of  claim 1 , further comprising purified poloxamer, Ammonium acetate, Benzalkonium chloride, Benzethonium chloride, Benzyl alcohol, Brij 35, Brij 97, Calcium gluceptate, ChlorobutanOL, Citric Acid, Cremophor EL, Deoxycholate, Diethanolamine, Ethanol, Gamma cyclodextrin, Glycerin, Lactobionic acid, Lysine, Magnesium chloride, Methylparaben, PEG 1000, PEG 300, PEG 3350, PEG 400, PEG 600, Poloxamer 188, Poloxamer 237, Poloxamer 338, Poloxmer 407, Polyoxyethylene 100 stearate, Polyoxyethylene 40 stearate, Polyoxyethylene 50 stearate, Polysorbate 20, Polysorbate 80, Povidone, Propylene Glycol, Sodium acetate, Vitamin E TPGS, Sodium benzoate, Sodium tartate, vegetable oil, soy bean oil, safflower oil, cottonseed oil, corn oil, sunflower oil, arachis oil, castor oil, olive oil, an ester of a medium or long-chain fatty acid, a palmitate, a glyceral ester, polyoxyl hydrogenated castor oil, ethoxylated ethers, polypropylene-polyethylene block co-polymers, phosphatides, egg phosphatide, soy phosphatide, glycerin, ascorbic acid, gentisic acid, or monosodium glutamate.  
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein said composition is: 
 a. an aqueous solution; or    b. a non-aqueous solution.    
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein said cysteine is of sufficient concentration to allow a no more than 10-fold increase in growth of each of  Staphylococcus aureus  ATCC 6538,  Escherichia coli  ATCC 8739,  Pseudomonas aeruginosa  ATCC 9027 and  Candida albicans  ATCC 10231 for at least 24 hours as measured by a test wherein a washed suspension of each said organism is added to a separate aliquot of said composition at approximately 50 colony forming units per ml, at a temperature in the range 20° C. to 25° C., whereafter said aliquots are incubated at 20° C. to 25° C. for 24 hours and thereafter tested for viable counts of said organism.  
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein said composition is administered: 
 a. intraveneous;    b. intramuscular; or    c. intrathecal.    
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the pH of said composition is: 
 a. between about 4.5 and about 9;    b. between about 5 and about 7;    c. between about 5 and about 6; or    d. between about 5.5 and about 6.    
     
     
         9 . A method of treating a patient by administering the pharmaceutical composition of  claim 1 .  
     
     
         10 . The pharmaceutical composition of  claim 1 , further comprising a local anesthetic.  
     
     
         11 . A pharmaceutical composition, comprising: 
 (a) propofol;    (b) a water immiscible solvent;    (c) a surfactant; and    (d) cysteine or a salt thereof.    
     
     
         12 . The pharmaceutical composition of  claim 11 , further comprising: 
 a. a tonicity modifier;    b. glycerol; or    c. a pH modifier.    
     
     
         13 . The pharmaceutical composition of  claim 11 , wherein said propofol is at a concentration of: 
 a. about 0.5 to 2.5% w/v;    b. about 0.5 to 1.5% w/v;    c. about 0.9 to 0.1% w/v; or    d. about 1% w/v.    
     
     
         14 . The pharmaceutical composition of  claim 11 , wherein said water immiscible solvent is: 
 a. selected from the group consisting of: 
 i) soybean oil;  
 ii) vegetable oil; and  
 iii) a medium or long-chain fatty acid; and  
   b. present at a concentration of: 
 i) from about 5 to about 15% w/v;  
 i) from about 8 to about 12% w/v;  
 i) from about 9 to about 11% w/v; or  
 i) about 10% w/v.  
   
     
     
         15 . The pharmaceutical composition of  claim 11 , wherein said surfactant is: 
 a. selected from the group consisting of: 
 i) polypropylene-polyethylene block co-polymers;  
 ii) egg phosphatide; and  
 iii) soy phosphatide; and  
   b. present at a concentration of: 
 i) from about 0.5 to about 5% w/v;  
 ii) from about 0.5 to about 2% w/v;  
 iii) from about 1 to about 1.5% w/v; or  
 iv) about 1.2% w/v.  
   
     
     
         16 . The pharmaceutical composition of  claim 11 , wherein said cysteine is: 
 a. cysteine; or a salt thereof; and    b. present at a concentration of: 
 i) from about 0.5 to about 5% w/v;  
 ii) from about 0.5 to about 2% w/v;  
 iii) from about 0.9 to about 1.5% w/v; or  
 iv) about 1% w/v.  
   
     
     
         17 . A pharmaceutical composition comprising propofol, one or more excipients, and a preservative selected from the list consisting of: 
 a. sodium ascorbate;    b. gentisic acid; and    c. monosodium glutamate.